Chapter 4: Protein Structure

The peptide bond is stronger than the ester bond. What structural feature of the peptide bond gives it additional bond strength?

Resonance structures give the peptide bond some double bond character.

List the levels of protein structure and give a brief description of each.

1. Primary—amino acid sequence from the N to C terminus. 2. Secondary—commonly occurring folds found in proteins, such as α-helix or β-sheet. 3. Tertiary—the overall three-dimensional structure of the protein chain. 4. Quaternary—the arrangement of subunits in a multi-subunit protein.

Consider the whole amino acid alanine at pH =7. How many atoms (including Hs) are found in the molecule?

13

Of the 20 common amino acids, how many have a chiral α-carbon?

19

How many possible protein primary structures are there for a tripeptide given the 20 amino acids?

20^3

How many β-turns or β-loops are required to construct a β-sheet composed of four antiparallel strands?

3

What is the minimum number of amino acids needed to make one turn of an α-helix?

4

How many possible unique triplet codons could there be in a genome?

64

Why is the amino acid proline not commonly found in α-helices or β-sheets? In what secondary structure might proline be commonly found?

Because of its cyclic nature, proline has more restricted φ and ψ angles. Also, because of its lack of an NH group on its backbone amine, proline cannot hydrogen bond to stabilize the helices or sheets. Proline can often be found in turns or loops connecting helices or strands.

The proteins collagen, silk fibroin, and hair keratin have all of the following in common, EXCEPT that they

are composed of α-helical structures.

Which of the following statements regarding protein domains is true? a. Each protein has one unique domain. b. Multiple domains require multiple subunits and a quaternary structure. c. A domain can be composed of smaller structural units called motifs. d. A domain is a region absent of α-helices and β-sheets.

c. A domain can be composed of smaller structural units called motifs.

Which of the following statements is true about α-helices? a. The center of the helix is an open channel. b. There are about seven amino acids per helical turn. c. The amide backbone dipoles line up in one direction. d. The helical backbone structure is stabilized by ionic interactions.

c. The amide backbone dipoles line up in one direction.

Which amino acid contains a hydroxyl group? a. valine b. cysteine c. threonine d. aspartate

c. threonine

The amino acid with the most hydrophobic side chain is a. asparagine. b. aspartate. c. valine. d. threonine.

c. valine.

All of the following are types of protein secondary structure EXCEPT a. β-sheets. b. α-helixes. c. β-helixes. d. β-turns.

c. β-helixes.

To what organic reaction class does peptide bond formation belong?

condensation

Which one of the following statements comparing alpha keratin and silk fibroin is true? a. Both have covalently cross-linked strands. b. Both are primarily α-helical in character. c. Both fibers are intracellularly located. d. Both fibers are heavily stabilized by hydrogen bonds.

d. Both fibers are heavily stabilized by hydrogen bonds.

Which statement regarding protein secondary structures is correct? a. β-strands allow α-helices to interact with one another. b. Protein α-helices alternate with β-strands in stabilizing protein structure. c. Protein α-helices are left handed, whereas β-sheets are right handed in arrangement. d. Protein α-helices and β-strands differ in that α-helices are stabilized by intrahelical hydrogen bonds, whereas β-strands are stabilized by hydrogen bonds across adjacent strands.

d. Protein α-helices and β-strands differ in that α-helices are stabilized by intrahelical hydrogen bonds, whereas β-strands are stabilized by hydrogen bonds across adjacent strands.

Which of the following statements about Ramachandran plots is true? a. They are good predictors of protein tertiary structure. b. They are needed to determine the secondary structure of a protein. c. They show equal distributions of φ and ψ angles for α-helical and β-sheet containing proteins. d. They show that β-sheets and α-helices occupy different φ and ψ angles.

d. They show that β-sheets and α-helices occupy different φ and ψ angles.

Which amino acid has the highest pKa? a. glutamate b. asparagine c. cysteine d. lysine

d. lysine

Cells deal with misfolded proteins by

degrading them to individual amino acids.

Of the three proposed models of globular protein folding, which one describes the initial formation of all secondary structures, followed by the arrangement of those secondary structures into a final tertiary structure?

framework model

At the interface between subunits of a protein with quaternary structure, which of the following interactions between amino acid side chains would contribute to the stability of the dimer?

glutamate-lysine.

The peptide bond

has a mix of single and double bond characters

Protein secondary structures such as α-helices and β-sheets are stabilized mainly by

hydrogen bond formation

Which interaction largely stabilizes protein secondary (2°) structures?

hydrogen bonding

Of the three proposed models of globular protein folding, which one describes formation of an initial disordered protein interior, followed next by ordering of secondary and tertiary structures?

hydrophobic collapse model

Cystic fibrosis results from the misfolding of proteins that never get the chance to properly insert into the membranes of lung epithelial cells and perform their function. This is generally referred to as a __________ disease.

loss-of-function protein folding

The protein fold known as the Rossman fold is found in proteins that commonly bind

nucelotides

In multi-subunit proteins, such as hemoglobin, the different subunits are usually bound to one another by all of the following EXCEPT

peptide bonds

A __________ mutation in a gene results in the least amount of damage to the resulting protein.

silent

All of the following are stabilizing forces in maintaining a stable protein tertiary (3°) structure, EXCEPT

temperature.

The φ and ψ angles are the

torsion angles on either side of the α-carbon.

What is the dominant secondary structure found in hair keratin?

α-helices

In a standard α-helix, __________ H bonds and __________ dipole moments are found per amino acid, which stabilizes the α-helical structure.

2; 1

Would a nonsense mutation in a gene encoding a protein be expected to result in a gain-of-function or a loss-of-function protein folding disease?

It might result in either disease or neither disease. It might be that a loss-of-function disease would be expected because the addition of a premature stop-codon would result in an incomplete and therefore nonfunctional protein. However, the incomplete protein could also aggregate and give rise to a gain-of-function folding disease. Finally, the protein may still function and fold in a relatively stable form depending on where the stop codon appeared.

Arrange the following in order of increasing complexity: secondary structure, tertiary structure, motif, and domain.

Secondary Structure → Motif → Domain → Tertiary Structure

Which gives rise to a favorable enthalpic (ΔS) driving force for protein folding?

The decrease in ordered water molecules as hydrophobic amino acids pack together.

What is a current hypothesis that explains the infectious nature of prion diseases?

The presence of an improperly folded prion protein promotes the misfolding of normal prion proteins.

What are the three-letter and one-letter abbreviations for the amino acid tyrosine?

Tyr, Y

Which of the following statements about the chamber-type chaperone protein GroEL-GroES is correct? a. GroEL-GroES requires the hydrolysis of multiple ATPs to assist in the folding of a protein. b. GroEL-GroES recycles misfolded proteins by recovering individual amino acids. c. GroEL-GroES assists in protein unfolding by hydrolyzing and remaking the protein peptide bonds. d. GroEL-GroES uses GroEL as a cap, trapping an unfolded protein in the GroES chamber.

a. GroEL-GroES requires the hydrolysis of multiple ATPs to assist in the folding of a protein.

Which statement about amino acids is true? a. Most common natural amino acids in proteins are L-amino acids. b. All naturally occurring amino acids in proteins are chiral. c. Most naturally occurring amino acids in proteins are D-amino acids. d. Naturally occurring amino acids in proteins occur as a mixture of enantiomers

a. Most common natural amino acids in proteins are L-amino acids.

Which of the following statements about β-sheet structures is true? a. The individual strands of all β-sheet structures are connected by turns, helices, or loops. b. All amino acid side chains in antiparallel and parallel β-sheet structures point to one side of the sheet. c. Parallel β-sheet structures have backbone amides that directly hydrogen bond between strands, whereas antiparallel β-sheets have hydrogen bonds that are offset. d. All β-sheet structures form a spiraling backbone chain.

a. The individual strands of all β-sheet structures are connected by turns, helices, or loops.

Which statement about the α-helix is true? a. The hydrophobic interior of α-helices is stabilized by the side chains of hydrophobic amino acids. b. The amino acid side chains point out to the sides with every third amino acid roughly lining up on one side of the helix. c. α-Helices have backbone amide groups that are hydrogen bonded to amino acid side chains. d. α-Helices have 5 amino acids per one turn of the helix.

b. The amino acid side chains point out to the sides with every third amino acid roughly lining up on one side of the helix.

The dipole moment associated with a peptide bond proceeds from which amide?

the H to the O atom

What is the difference between clamp-type and chamber-type chaperone proteins?

they are shaped differently

Christian Anfinsen showed in a famous experiment that it is possible to unfold a protein and refold it to obtain a functional protein. Which two reagents were used in this experiment to unfold the protein?

urea and β-mercaptoethanol

List reagents and conditions that denature proteins.

Reagents: chaotropic agents such as urea, acids and bases, organic solvents such as ethanol, soaps or detergents, salts, reducing agents such as β-mercaptoethanol. Conditions: temperature, mechanical stress, pressure, pH.

At what point does the isoelectric point or pI occur?

at the pH when all negative charges on a zwitterion counter the positive charges

Which linear sequence of bonded atoms can be found in the backbone of polypeptides? a. C-N-N-C b. C-C-N-C c. N-C-C-C d. C-O-C-N

b. C-C-N-C

How many different protein folds are recognized in the formal system of organization, referred to as SCOP: Structure Organization of Proteins?

>1000

Describe generally how a gain-of-function protein folding disease can lead to cell death.

A gain-of-function folding disease generally results from the aggregation of misfolded proteins. The protein aggregates interfere with normal cellular function. The misfolded proteins can result from mutations in a gene, such as in Huntington's disease, or from the mistreatment of normal proteins, such as in Alzheimer's disease.

In the multi-subunit protein family called immunoglobulins, the different subunits are held together by both covalent and noncovalent forces. What are the covalent forces that hold subunits together in immunoglobulins?

Cysteine disulfide bonds covalently bond together the heavy and light subunits.

What is the peptide sequence Asp-Gln-Gly-Ser, using one-letter abbreviations for the amino acids?

DQGS

Which of the following statements about the clamp-type chaperone protein Hsp70 is correct?

Hsp70 uses ATP binding and hydrolysis energy to assist in the folding of a protein.

In the famous experiment where Christian Anfinsen unfolded and refolded the protein RNaseA, in what order was the denaturant and reductant removed to give an inactive protein? Why was the protein inactive?

If the β-mercaptoethanol was removed first, before the urea, the protein tended to form incorrect inter- and intramolecular disulfide bonds while in the unfolded state. The incorrect disulfide bonds stabilized largely misfolded and therefore inactive proteins.

Describe the proposed model of globular protein folding called the nucleation model.

In the nucleation model of globular protein folding, a small localized region of the unfolded protein folds first with the correct tertiary structure. This region then serves as a center of growth around which the remaining secondary and tertiary structures fold.

The chirality of naturally occurring amino acids in proteins is

L

An α-helix has the sequence: NH3+-Ser-Glu-Gly-Asp-Trp-Gln-Leu-His-Val-Phe-Ala-Lys-Val-Glu-COO-. The carbonyl oxygen (in the peptide bond) of the histidine residue is hydrogen bonded to the amide nitrogen of

Lys

Trace directly the covalently bonded backbone atoms from the N to C terminus of a dipeptide. Which atoms are found in this trace?

NCCNCC

What do Ramachandran plots show?

Only some ψ and φ angles are commonly found in proteins.

What is a difference between parallel and antiparallel β-sheet secondary structures?

Parallel β-sheets require a larger loop connecting together the individual peptide strands in the sheet.

After analyzing all the structures of proteins found in the Protein Data Bank, scientists have found that four general classes of protein structures exist, based on their secondary structure themes. Name the four classes of general protein structures.

Predominantly α-helical, predominantly β-sheet, intermixed α-helix and β-sheet, and domains of α-helix adjacent to domains of β-sheet

In the Anfinsen experiment with the unfolding of RNaseA, what order could the chemical reagents be removed in order to achieve an inactive protein?

Remove reductant first and denaturant second.

What is believed to be the underlying cause of prion protein plaque formation?

The PrPSc proteins are misfolded and aggregated from PrPc proteins.

The essential amino acids in adult humans are those that are required in our diet because of a lack of the biosynthetic pathway in our cells. The single-letter abbreviations for these amino acids are WVMILKFHT. Name these amino acids.

Tryptophan, valine, methionine, isoleucine, leucine, lysine, phenylalanine, histidine, and threonine

Which amino acid side chain from the list below is the most polar? a. Gln b. Ala c. Leu d. Phe

a. Gln

Which of the following are negatively charged amino acids at pH = 7? a. Glu, Asp b. Gln, Asn c. Thr, Tyr d. Cys, Asn

a. Glu, Asp

The amino acid with the neutral side chain at neutral pH is a. asparagine. b. aspartate. c. arginine. d. glutamate.

a. asparagine.

It is important for cells to degrade misfolded proteins. If misfolded proteins are not degraded, the misfolded proteins may

aggregate and interfere with normal cellular function.

Protein tertiary structures

are often disrupted by the either very low pH or very high pH values as a result of alterations in the ionization states of acidic or basic amino acids.

A polypeptide has a high pI value. Which amino acids might comprise it?

arginine and lysine residues

Which of the following statements about α-helices and β-sheets are FALSE? a. They are both incompatible with the amino acid proline. b. They both interact with other protein elements through amino acid side chains that stick out. c. They both contain a recurring pattern of hydrogen bonds from one peptide bond to another peptide bond. d. They both give rise to similar tertiary structures.

d. They both give rise to similar tertiary structures.

Which stabilizing force in protein tertiary structures is a covalent bonding force?

disulfide bonding